EP-A-0 319 329 discloses that compounds of the following formula (A') and salts thereof are useful as bioreductive drugs for treating tumours: ##STR3## wherein X represents a nitro-substituted aromatic or hereto-aromatic group with a one-electron reduction potential at pH 7 of from -250 to -500 mV; each of R'.sub.1 to R'.sub.5 independently represents hydrogen or an alkyl, hydroxyalkyl, aryl, aralkyl or alkaryl group; m is 0 or 1; n is 1 or 2; and Z' represents a leaving group which has the potential for expulsion via an intramolecular cyclisation reaction.
A preferred bioreductive compound disclosed in EP-A-0 319 329 for treating tumours is 1-(2-nitro-1-imidazolyl)-3-(2-bromoethylamino)-2-propanol hydrobromide (RB6145).
Nitric oxide (NO) synthase inhibitors have been proposed as useful for treating a variety of diseases. NO synthase produces NO from L-arginine. Local release of NO from the vascular endothelium causes dilation of blood vessels; for review see Moncada et al (1991) Pharmacol. Rev. 43, 109-141. The inhibition of NO synthase by compounds such as L-arginine analogues causes constriction of blood vessels, which results in a localised reduction of blood perfusion and/or increased blood pressure (Thiemermann (1991) Eicosanoids 4, 187-202).
We have recently studied the effects of enhancing or reducing NO availability in solid tumours (Wood et al (April 1993) Biochemical and Biophysical Research Communications 192, 505-510). We discovered that the NO synthase inhibitor nitro-L-arginine causes a sustained reduction in the amount of oxygen in the tumour. In contrast, we discovered that the NO donor SIN-1 increases tumour oxygenation.